The primary objectives of this project are to discover and study naturally occurring delayed-type iso-hypersensitivities towards heritable iso-antigens and to determine the function of this type phenomenon. From this laboratory we have described three instances of such iso-reactivity. The first, in guinea pigs is revealed in vivo by delayed dermal reactions to an iso-antigenic serum factor (SF) and in vitro by inhibiting macrophage migration with SF as well as by lymphocyte blastogenesis that is triggered by SF. The second, in mice, is shown by neonatal T cells that replicate in the presence of mitomycin-treated, isogeneic, adult spleen cells. The third, also in mice, is shown by adult lymph node cells that blast towards mitomycin- treated autochtonous, as well as isologous adult spleen cells. In the latter two systems we seek to further elucidate how the murine differentiation B cell antigens are acquired, whether they exist on the same cell, whether splenic influence determines their presence, whether they are T cell product acceptors, and whether they function in antibody synthesis. Another objective is to investigate the immunological regulatory effects exerted by non-ionic dextran toward other unrelated antigens. Both humoral antibody synthesis and delayed hypersensitivity onset and severity can be altered by giving dextran at different times relative to antigen. Furthermore, T cell and B cell responses to mitogens can be markedly enhanced by in vivo administered dextran. Both B and T cell enhancing and T cell suppressive factors have been chromatographically separated from supernatants of splenic T cells triggered in vivo with dextran. We wish to determine whether any of the factors correlate with T replacing factor and which subset of T cells dextran acts upon. We are pursuing this work from the viewpoints of (a) understanding initiation and prevention of immune responses, as well as (b) learning about shifts in synthesis of immunoglobulins M and G.